Mexiletine is extracted with an organic solvent from serum at neutral or basic pH, but pH 10.4 is optimal for minimal interference from other drugs and maximal recovery. The organic extract is acidified and then evaporated under a stream of N(2). The residue is taken up in mobile phase and chromatographed by reverse-phase high-performance liquid chromatography (HPLC). Mexiletine is detected by absorbance at 210 nm and quantified by peak height ratios relative to an internal standard, p-chlorodisopyramide.(Mastropaolo W, Holmes DR, Osborn MJ, et al: Improved liquid-chromatographic determination of mexiletine, an antiarrhythmic drug, in plasma. Clin Chem 1984;30:319-322)